Mammary Tumor Regression Elicited by Wnt Signaling Inhibitor Requires IGFBP5
| Autor: | Bob Y. Liu, Irina Soloviev, James A. Ernst, Paul Polakis, Chie Sakanaka, XiaoDong Huang, Peter Chang |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
medicine.medical_specialty Recombinant Fusion Proteins medicine.medical_treatment Mammary gland Paracrine Communication Antineoplastic Agents Wnt1 Protein Adenocarcinoma Biology Mice Mammary tumor virus Cell Line Tumor Internal medicine medicine Animals Involution (medicine) Wnt Signaling Pathway Mammary gland involution beta Catenin Mammary tumor Growth factor Wnt signaling pathway Mammary Neoplasms Experimental Mice Inbred C57BL medicine.anatomical_structure Endocrinology Mammary Tumor Virus Mouse Oncology Cancer research Female Insulin-Like Growth Factor Binding Protein 5 |
| Zdroj: | Cancer Research. 72:1568-1578 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Wnt ligand–driven tumor growth is inhibited by the soluble Wnt inhibitor Fzd8CRD, but the mechanism through which this effect is mediated is unknown. In the MMTV-Wnt1 mouse model, regression of mammary tumors by Fzd8CRD treatment coincides with an acute and strong induction of insulin-like growth factor (IGF)–binding protein IGFBP5, an antagonist of IGF signaling that mediates involution of mammary gland in females after offspring are weaned. In this study, we show that repression of this IGF inhibitory pathway is crucial for Wnt-driven growth of mammary tumors. We found that IGFBP5 regulation was mediated by the β-catenin–dependent Wnt pathway. Wnt, in addition to IGF ligands, facilitated tumor growth by paracrine communication among tumor cells. In addition, Fzd8CRD caused precocious induction of IGFBP5 in normal mammary glands undergoing involution, implying an acceleration of the involution process by inhibition of Wnt signaling. The molecular and phenotypic parallel between tumor regression and mammary gland involution suggests that Wnt-driven mammary tumors use the same growth mechanism as proliferating normal mammary glands. Cancer Res; 72(6); 1568–78. ©2012 AACR. |
| Databáze: | OpenAIRE |
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